It had been providing safety and communications support for another helicopter involved in an overnight rescue operation when contact was lost at around 1am.
One of the four crew members on board was located and pulled from the water at around 7am and was taken to hospital in a critical condition.
Coastguard helicopters from Sligo and Shannon, lifeboats, local fishing vessels and Air Corps maritime patrol aircraft are involved in ongoing searches off the coast of County Mayo.
A spokesperson for the Irish coastguard said the missing helicopter had been providing cover in the evacuation of a crewman on a UK-registered fishing vessel who required urgent medical attention, approximately 150 miles west of Eagle Island.
“Owing to the distance involved, safety and communication support, known as Top Cover, was provided by the second Coast Guard helicopter, the Dublin based R116,” he said.
“The search operation is being coordinated by the Coast Guard Rescue Coordination Centre in Malin Head.
“Both helicopters refuelled at Blacksod prior to transiting to the scene.”
Declan Geoghegan, the Irish coastguard’s operations manager, said debris believed to belong to the helicopter had been found in the water.
“We don’t know what happened and obviously there will be an air accident investigation into it,” he told BBC Radio Foyle.
“We’ll continue to search for the missing crew members until such time as we have recovered them and the flight recorder.”
Shane Ross, the Irish transport minister, expressed his ”deep concern“ over the Dublin-based helicopter’s disappearance.
“As the search for the Dublin-based helicopter R116 is currently under way I would like to express my sincere support and sympathies for all those involved, particularly those family members who are awaiting news of their loved ones,” he said.
“This is an extremely difficult time for all concerned.”
No storms or extreme weather conditions were reported in the area at the time of the aircraft’s disappearance.